SIX6
Chr 14ARSIX homeobox 6
Also known as: MCOPCT2, ODRMD, OPTX2, Six9
SIX6 encodes a homeobox transcription factor involved in eye development. Biallelic mutations cause optic disc anomalies with retinal and/or macular dystrophy, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.595), consistent with its role in ocular development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
177 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 2 | 12 | 0 | 15 |
Likely Pathogenic | 4 | 1 | 3 | 0 | 8 |
VUS | 5 | 61 | 18 | 3 | 87 |
Likely Benign | 0 | 1 | 9 | 42 | 52 |
Benign | 0 | 1 | 3 | 1 | 5 |
Conflicting | — | 9 | |||
| Total | 10 | 66 | 45 | 46 | 176 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SIX6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Study Evaluating Safety Pharmacokinetics and Pharmacodynamics of AUR112 in Patients With Relapsed Advanced Lymphoma
RECRUITINGThe Impact of a Race-Based Stress Reduction Intervention
RECRUITINGTesting the Combination of Anti-cancer Drugs Actimab-A and Cemiplimab (REGN2810) to Improve Outcomes for Patients With Recurrent Glioblastoma
NOT YET RECRUITINGThe Role of Universal Cancer Only Marker SIX6 in Diagnosing Non-Muscle Invasive Bladder Cancer
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools